Title

Author

Date of Award

2006

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Carleen M. Collins, Committee Chair

Abstract

Plague, or the Black Death, is a zoonotic disease that is spread from mammal to mammal by fleas. This mode of transmission demands that the causative agent of this disease, Yersinia pestis, be able to circumvent the host defense systems of both mammals and insects. In recent years the complete genome sequence of a number of Y. pestis strains have been determined. This sequence information indicates that Y. pestis contains a cluster of genes with homology to insecticidal toxin encoding genes of the insect pathogen Photorhabdus luminescens. Here we demonstrate that Y. pestis KIM strains transcribe these insecticidal-like toxin genes, and produce the encoded proteins. Production of the locus-encoded proteins was dependent on the presence of a gene (yitR) encoding a member of the LysR family of transcriptional activators. A large complex that contains each locus-encoded protein (YitA, B, C, and YipA and B) was isolated from Y. pestis, however biological activity of this complex has not been demonstrated. The insecticidal-like toxins were secreted by the virulence plasmid-encoded type III secretion system in a calcium and temperature dependent manner. Translocation of one protein that is a putative tyrosine phosphatase, YipB, was demonstrated into both mammalian macrophage and insect cells. In conclusion, a new class of Y. pestis type three secreted and translocated proteins has been identified. We hypothesize that these proteins function to promote transmission of and infection by Y. pestis.